1. Field of the Invention
The present invention relates to niacin-peptides having skin whitening effect and uses thereof.
2. Description of the Related Art
The color of human skin varies due to numerous factors involving seasons, human races and sex. The skin color is mainly governed by the amount of melanin, carotene and hemoglobin in which melanin is the most crucial factor. Melanin synthesized in melanocytes in the skin basal layer is transferred to adjacent keratinocytes and then is responsible for the color of human skin. The lack of melanin may induce skin lesions such as leukoplakia whereas an excess production of melanin may generate freckles and blemishes. Melanin is formed by tyrosinase-involving reactions on tyrosine. Since the tyrosinase becomes more active by ultraviolet rays, the skin color becomes darker upon exposure of the skin to sun lights. Cosmetics for skin whitening have established large market in Korea and Japan, most of which contain a mixture of substances having inhibitory effects on the tyrosinase activity.
The reasons why Asians skin is more vulnerable to pigmentation and aging have been completely not suggested yet, while the activities of numerous enzymes implicated in melanogenesis and skin darkness were recently reported. The potential substances capable of brightening dark skin have been usually known to inhibit both melanogenesis and implicated enzymes.
Conventional ingredients as tyrosinase inhibitors introduced into skin whitening cosmetics includes ascorbic acid (Vitamin C) and its derivatives, plant extracts involving Morus Alba Bark extract, green tea extract, aloe extract, Scutellaria Laterifolia extract and so forth, kojic acid, arbutin, oil-soluble glycyrrhiza extract and niacinamide. However, various plant extracts are very likely to show instability and non-lasting effects, when they are introduced into products. Also, their inhibitory effect on the tyrosinase activity is likely to be negligent. Kojic acid conventionally used as tyrosinase inhibitors causes allergic reactions (Nakagawa M. et. al., Contact Dermatitis, 43:PP9-3(1995)) and has serious production problems in which it has to be used in relatively excessive amounts (e.g., 2%) due to its instability in products.
Niacinamide approved by KFDA (Korea Food & Drug Administration) as a functional skin whitening material is water-soluble Vitamin B3 also known as nicotinamide. Niacinamide essential for human body is contained in foods such as green vegetables and cereals. The necessity of niacinamide for healthy skin has been recognized since the early 20th century. The deficient of Vitamin B3 in diets results in the pellagra causing severe skin lesions; therefore, niacinamide has been also called as Vitamin PP to prevent the disease.
Niacinamide has been reported not to inhibit activity of tyrosinase and dopaoxidase unlike other conventional melanogenesis inhibitors with direct inhibitory effects on melanogenesis, and further not to suppress melanogenesis in cultured melanocytes. Melanosomes carrying melanin generated in melanocytes localized in the basal layer are transferred to keratinocytes through dendrites. Niacinamide has been suggested to only block movement of melanosomes onto the skin surface. It has been well-known for maintenance of bright skin by decreasing melanin movement from melanocytes to keratinocytes by 68%. However, niacinacetate as one of intermediates for niacinamide synthesis remains around 20-100 ppm in the purification process of niacinamide with higher purity. The residual niacinacetate has been reported to show high cytotoxicity.
In spite of numerous attempts to develop skin whitening products using peptides, their skin whitening effects have not been satisfactory yet. Vitamin C-peptide complex and hydro quinone-peptide complex developed to maximize skin whitening effects are problematic in terms of their preparation and cost, resulting in limited application to cosmetic market.
Throughout this application, various patents and publications are referenced and citations are provided in parentheses. The disclosure of these patents and publications in their entities are hereby incorporated by references into this application in order to more fully describe this invention and the state of the art to which this invention pertains.